Immunocore presents initial multiple ascending dose data for HIV functional cure candidate in an oral presentation at CROI 2025
Immunocore (NASDAQ: IMCR) has presented initial data from the multiple ascending dose (MAD) portion of its Phase 1/2 STRIVE trial for IMC-M113V, a functional HIV cure candidate. The study included 16 HIV-positive participants across three dose cohorts (60 mcg, 120 mcg, and 300 mcg).
Key findings show that IMC-M113V was well-tolerated with no serious adverse events. The 300 mcg cohort showed promising results, with 2 out of 5 patients demonstrating viral control. Notably, these patients maintained viral loads around 200 c/mL at week 8, significantly better than the historical rate of 5%.
The trial revealed dose-dependent viral control after antiretroviral treatment interruption, with some patients showing reduced CD4+ T cell-associated HIV Gag RNA, indicating a reduction in active virus reservoir. Two patients remained off antiretroviral treatment for the entire 12-week interruption period, with one patient showing viral reduction to <50 c/mL at week 12 - an outcome typically seen in <1% of cases.
Immunocore (NASDAQ: IMCR) ha presentato dati preliminari dalla parte a dosi ascendenti multiple (MAD) del suo studio di Fase 1/2 STRIVE per IMC-M113V, un candidato funzionale per la cura dell'HIV. Lo studio ha incluso 16 partecipanti HIV-positivi suddivisi in tre coorti di dose (60 mcg, 120 mcg e 300 mcg).
I risultati chiave mostrano che IMC-M113V è stato ben tollerato senza eventi avversi gravi. La coorte da 300 mcg ha mostrato risultati promettenti, con 2 pazienti su 5 che hanno dimostrato controllo virale. È interessante notare che questi pazienti hanno mantenuto cariche virali intorno a 200 c/mL alla settimana 8, significativamente migliori rispetto al tasso storico del 5%.
Lo studio ha rivelato controllo virale dipendente dalla dose dopo l'interruzione del trattamento antiretrovirale, con alcuni pazienti che hanno mostrato una riduzione dell'RNA Gag dell'HIV associato alle cellule T CD4+, indicando una riduzione del serbatoio virale attivo. Due pazienti sono rimasti senza trattamento antiretrovirale per l'intero periodo di interruzione di 12 settimane, con un paziente che ha mostrato una riduzione virale a <50 c/mL alla settimana 12 - un risultato tipicamente osservato in <1% dei casi.
Immunocore (NASDAQ: IMCR) ha presentado datos iniciales de la parte de dosis ascendentes múltiples (MAD) de su ensayo de Fase 1/2 STRIVE para IMC-M113V, un candidato funcional para la cura del VIH. El estudio incluyó a 16 participantes VIH-positivos en tres cohortes de dosis (60 mcg, 120 mcg y 300 mcg).
Los hallazgos clave muestran que IMC-M113V fue bien tolerado sin eventos adversos graves. La cohorte de 300 mcg mostró resultados prometedores, con 2 de 5 pacientes demostrando control viral. Notablemente, estos pacientes mantuvieron cargas virales alrededor de 200 c/mL en la semana 8, significativamente mejor que la tasa histórica del 5%.
El ensayo reveló control viral dependiente de la dosis después de la interrupción del tratamiento antirretroviral, con algunos pacientes mostrando una reducción del ARN Gag del VIH asociado a células T CD4+, indicando una reducción en el reservorio viral activo. Dos pacientes permanecieron sin tratamiento antirretroviral durante todo el período de interrupción de 12 semanas, con un paciente mostrando reducción viral a <50 c/mL en la semana 12 - un resultado que típicamente se observa en <1% de los casos.
Immunocore (NASDAQ: IMCR)는 IMC-M113V의 1/2상 STRIVE 시험의 다중 상승 용량(MAD) 부분에서 초기 데이터를 발표했습니다. 이 연구에는 세 가지 용량 집단(60 mcg, 120 mcg, 300 mcg)에서 16명의 HIV 양성 참가자가 포함되었습니다.
주요 결과는 IMC-M113V가 잘 견딜 수 있었다는 것으로, 심각한 부작용은 없었습니다. 300 mcg 집단은 5명 중 2명이 바이러스 조절을 보여주는 등 유망한 결과를 보였습니다. 특히, 이 환자들은 8주차에 200 c/mL 주변의 바이러스 부하를 유지하여 역사적 비율인 5%보다 훨씬 나은 결과를 보였습니다.
시험 결과는 항레트로바이러스 치료 중단 후 용량 의존적인 바이러스 조절이 나타났으며, 일부 환자는 CD4+ T 세포와 관련된 HIV Gag RNA의 감소를 보여주어 활성 바이러스 저장소의 감소를 나타냈습니다. 두 명의 환자는 12주 간의 치료 중단 기간 동안 항레트로바이러스 치료를 받지 않았으며, 한 환자는 12주차에 <50 c/mL로 바이러스 감소를 보여주었습니다 - 이는 일반적으로 <1%의 경우에서 관찰되는 결과입니다.
Immunocore (NASDAQ: IMCR) a présenté des données préliminaires de la partie à doses ascendantes multiples (MAD) de son essai de Phase 1/2 STRIVE pour IMC-M113V, un candidat fonctionnel à la guérison du VIH. L'étude a inclus 16 participants VIH-positifs répartis en trois cohortes de dose (60 mcg, 120 mcg et 300 mcg).
Les résultats clés montrent qu'IMC-M113V a été bien toléré sans événements indésirables graves. La cohorte de 300 mcg a montré des résultats prometteurs, avec 2 patients sur 5 démontrant un contrôle viral. Il est à noter que ces patients ont maintenu des charges virales autour de 200 c/mL à la semaine 8, ce qui est significativement mieux que le taux historique de 5%.
L'essai a révélé un contrôle viral dépendant de la dose après interruption du traitement antirétroviral, certains patients montrant une réduction de l'ARN Gag du VIH associé aux cellules T CD4+, indiquant une réduction du réservoir viral actif. Deux patients sont restés sans traitement antirétroviral pendant toute la période d'interruption de 12 semaines, un patient montrant une réduction virale à <50 c/mL à la semaine 12 - un résultat généralement observé dans <1% des cas.
Immunocore (NASDAQ: IMCR) hat erste Daten aus dem Teil mit mehrfachen aufsteigenden Dosen (MAD) seiner Phase 1/2 STRIVE-Studie für IMC-M113V, einen funktionalen HIV-Heilungskandidaten, präsentiert. Die Studie umfasste 16 HIV-positive Teilnehmer in drei Dosisgruppen (60 mcg, 120 mcg und 300 mcg).
Die wichtigsten Ergebnisse zeigen, dass IMC-M113V gut verträglich war und keine schwerwiegenden unerwünschten Ereignisse auftraten. Die 300 mcg Gruppe zeigte vielversprechende Ergebnisse, wobei 2 von 5 Patienten eine virale Kontrolle demonstrierten. Bemerkenswert ist, dass diese Patienten die Viruslast in der 8. Woche bei etwa 200 c/mL hielten, was deutlich besser ist als die historische Rate von 5%.
Die Studie ergab dosisabhängige virale Kontrolle nach Unterbrechung der antiretroviralen Behandlung, wobei einige Patienten eine reduzierte CD4+ T-Zell-assoziierte HIV Gag RNA zeigten, was auf eine Verringerung des aktiven Virusreservoirs hinweist. Zwei Patienten blieben während des gesamten 12-wöchigen Unterbrechungszeitraums ohne antiretrovirale Behandlung, wobei ein Patient eine Virusreduktion auf <50 c/mL in der 12. Woche zeigte - ein Ergebnis, das typischerweise in <1% der Fälle zu beobachten ist.
- Dose-dependent viral control achieved in higher dose cohorts
- 2 of 5 patients at 300 mcg showed viral control, exceeding historical 5% rate
- Evidence of reduced active virus reservoir in some patients
- Strong safety profile with no serious adverse events
- Lower dose cohort (60 mcg) showed no viral control
- One participant withdrew from 300 mcg cohort (though unrelated to treatment)
- Mild cytokine release syndrome observed in 300 mcg cohort
Insights
Immunocore's presentation of multiple ascending dose (MAD) data for IMC-M113V shows promising progress in their HIV functional cure strategy. The safety profile is particularly encouraging with no serious adverse events or dose-limiting toxicities across all tested doses (60-300 mcg). The mild cytokine release syndrome observed in the highest dose cohort resolved quickly and aligns with the expected mechanism of action.
Most significant is the dose-dependent efficacy signal - with viral control observed in 0/5 patients at 60 mcg, 1/5 at 120 mcg, and 2/5 at 300 mcg. Two patients maintained controlled viremia (<200 copies/mL) through the entire 12-week treatment interruption period. This exceeds historical control rates of <1-5% for comparable HIV treatment interruption studies.
The observed reduction in HIV Gag RNA and trend toward reduction in intact HIV DNA suggest real impact on the viral reservoir - the central challenge in HIV cure research. These biomarker changes provide mechanistic support for the clinical observations of viral control.
As the first T-cell receptor bispecific therapy targeting HIV in clinical trials, IMC-M113V represents a novel modality in the HIV functional cure landscape. The continued dose escalation suggests potential for improved response rates at higher doses. This early data positions Immunocore's approach as technically differentiated with proof-of-mechanism in humans.
These Phase 1/2 STRIVE trial results represent a meaningful scientific and potential commercial advancement for Immunocore's HIV program. The dose-dependent viral control data suggests a clear pharmacological effect, with the 300 mcg dose showing the most promising efficacy signals - important validation for Immunocore's T cell receptor platform in infectious disease applications beyond their existing oncology franchise.
The safety profile appears manageable, with only mild and transient cytokine release syndrome at the highest dose - an expected on-target effect that's well understood in redirected T cell therapies. This favorable safety/efficacy balance supports continued dose escalation, potentially yielding improved response rates.
Most commercially significant is the functional cure potential demonstrated by patients maintaining viral control through the 12-week treatment interruption. Currently, people living with HIV require lifelong daily antiretroviral therapy, representing a massive market opportunity for any therapy enabling treatment holidays or complete ART discontinuation.
While early-stage, these results meaningfully de-risk Immunocore's HIV program, expanding their pipeline value beyond their commercial KIMMTRAK product. The company's unique platform approach to both cancer and infectious diseases creates potential synergies in manufacturing and clinical development. The continued dose escalation and planned expansion cohorts should provide additional validation within the next 12-18 months, representing near-term catalysts for this program.
Immunocore presents initial multiple ascending dose data for HIV functional cure candidate in an oral presentation at CROI 2025
IMC-M113V was well tolerated, with no dose-limiting toxicities
Signals of dose-dependent reduction in active reservoir, and viral control after complete antiretroviral treatment interruption in some PLWH
Enrollment in MAD portion of the trial continues with higher doses being evaluated
(OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & GAITHERSBURG, Md., US, 10 March 2025) Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, has today shared initial data from the multiple ascending dose (MAD) portion of its Phase 1/2 STRIVE trial of IMC-M113V, its functional cure candidate for human immunodeficiency virus (HIV).
The data, presented in an oral session at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025, in San Francisco, shows that IMC-M113V – the first T cell receptor bispecific therapy to target HIV in the clinic – is well tolerated and shows signals of dose-dependent viral control after antiretroviral treatment (ART) is interrupted. The MAD portion of the trial continues and is evaluating higher doses, to be followed by expansion cohorts at one or more doses.
“I am encouraged by the safety profile and initial signals of anti-viral activity of IMC-M113V in the Phase 1/2 trial. It is uncommon to be able to interrupt ART for 12 weeks or longer, with the vast majority of people showing viral rebound by 4 weeks,” said Dr. Beatriz Mothe, Associate Investigator, HIV Unit, Infectious Diseases Department, IrsiCaixa, Hospital Germans Trias i Pujol, Barcelona. “I look forward to further data from the trial at higher doses, as part of wider efforts to find solutions that could enable people with HIV to remain healthy without lifelong antiretroviral treatment.”
Initial MAD data
The MAD portion of the Phase 1/2 dose escalation trial, reported at CROI, included 16 people living with HIV (PLWH) who were stable on ART. Enrollment excluded individuals who had started ART less than 12 weeks after acquiring HIV. While continuing ART, three sequential cohorts evaluated weekly IV infusions of IMC-M113V up to doses of 60 mcg (n=5), 120 mcg (n=5), and 300 mcg (n=6) administered over 12 weeks, followed by analytical treatment interruption (ATI) for up to 12 weeks, after which participants resumed their prior ART regimen.
All doses were well tolerated and no serious adverse events (AEs) or dose limiting toxicities were observed. Mild (Grade 1) cytokine release syndrome, consisting of fever alone that resolved within 4 hours, was observed in five of the six PLWH in the 300 mcg cohort when receiving their first 300 mcg dose. There were no discontinuations due to AEs. One person withdrew prior to completing the dose schedule in the 300 mcg cohort for reasons unrelated to IMC-M113V.
Dose-dependent increases in serum cytokines were observed, consistent with the mechanism of action, with the highest levels of T cell-derived cytokines at 300 mcg.
In the 15 evaluable PLWH, delayed viral rebound and/or viremia control at any point during ATI was observed in 0 of 5 PLWH at 60 mcg, 1 of 5 at 120 mcg, and 2 of 5 at 300 mcg. The 3 PLWH with evidence of viral control had a viral load of approximately 200 c/mL at week 8. The historical rate for this observation is
In the 3 PLWH with evidence of viral control, the pattern consisted of initial viral rebound followed by viral reduction to approximately 200 c/mL, including 1 PLWH at 300 mcg who had initial viremia to >104 c/mL before subsequent decrease to <50 c/mL at week 12. This observation of initial viremia followed by control at week 12 is typically observed in <
There was also a reduction in CD4+ T cell-associated HIV Gag RNA in some PLWH during treatment, indicating a reduction in the active virus reservoir, which was quantified at weeks 1, 7 and 13. A trend of reduction in intact HIV DNA was also observed post-treatment in a preliminary analysis of 6 people treated at the two highest doses.
IMC-M113V and the STRIVE trial
IMC-M113V utilizes a T cell receptor that binds to an HLA-A*02:01-Gag complex on HIV-infected immune cells. An anti-CD3 effector arm of the molecule then recruits T cells to destroy CD4+ cells containing integrated HIV DNA, known as the reservoir.
The objectives of the first-in-human Soluble T cell Receptors in Viral Eradication (STRIVE) Phase 1/2 trial are to establish safe dose regimens administered alongside ART and to quantify antiviral activity, measured through post-treatment viral control (<200 c/ml) after ART withdrawal.
The Company presented initial Phase 1 safety and pharmacodynamic activity data from the single-ascending dose portion of the trial in February 2023. The data demonstrated IMC-M113V was well tolerated with no serious adverse events. Expected markers of T cell activation were observed in half of people (n=10) who received a maximum dose of 15 mcg.
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About ImmTAV® molecules for infectious diseases
ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules are novel bispecifics that are designed to enable the immune system to recognize and eliminate virally infected cells.
Immunocore is advancing clinical candidates to achieve functional cure for patients with HIV and hepatitis B virus (HBV). The Company aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. For the treatment of HBV, the Company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic HBV.
About Immunocore
Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including numerous active clinical and pre-clinical programs in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.
Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may”, “will”, “believe”, “expect”, “plan”, “anticipate”, “aim”, “continue”, “target” and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding the therapeutic potential of Immunocore’s product candidates, including IMC-M113V; and expectations regarding the design, progress, timing, enrollment, randomization, scope, expansion, funding, and results of Immunocore’s existing and planned clinical trials, including the IMC-M113V STRIVE Phase 1/2 clinical trial and expansions into additional cohorts. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, the impact of worsening macroeconomic conditions on the Company’s business, financial position, strategy and anticipated milestones, including Immunocore’s ability to conduct ongoing and planned clinical trials; Immunocore’s ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products; Immunocore’s ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK; Immunocore’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; Immunocore’s ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; Immunocore’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore’s need for and ability to obtain additional funding, on favorable terms or at all, including as a result of worsening macroeconomic conditions, including changes in inflation and interest rates and unfavorable general market conditions, and the impacts thereon of the war in Ukraine, the conflict in the Middle East, and global geopolitical tension; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; and the success of Immunocore’s current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in Immunocore’s filings with the Securities and Exchange Commission, including Immunocore’s most recent Annual Report on Form 10-K for the year ended December 31, 2024 filed with the Securities and Exchange Commission on February 26, 2025, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the SEC. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law.
Contact Information
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E: sebastien.desprez@immunocore.com
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Investor Relations
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1 Gunst, J.D., Gohil, J., Li, J.Z. et al. Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies. Nat Commun 16, 906 (2025).
FAQ
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